2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid has a strong activity for inhibiting xanthine oxidase or a uric acid decreasing action, and it is expected to be a therapeutic agent for gout or hyperuricemia, as has been described in International Publication WO92/09279.
In International Publication WO99/65885, there are described following six crystal polymorphs of 2-(3-cyano-4-isobutyloxyphehyl)-4-methyl-5-thiazole carboxylic acid, i.e., a polymorph which shows an X-ray powder diffraction pattern having specific peaks at a reflection angle 2θ, of about 6.62°, 7.18°, 12.80°, 13.26°, 16.48°, 19.58°, 21.92°, 22.68°, 25.84°, 26.70°, 29.16° and 36.70° (crystal A).;
a polymorph which has specific peaks at a reflection angle 2θ of about 6.76°, 8.08°, 9.74°, 11.50°, 12.22°, 13.56°, 15.76°, 16.20°, 17.32°, 19.38°, 21.14°, 21.56°, 23.16°, 24.78°, 25.14°, 25.72°, 26.12°, 26.68°, 27.68° and 29.36° (crystal B);
a polymorph which has specific peaks at a reflection angle 2θ of about 6.62°, 10.82°, 13.36°, 15.52°, 16.74°, 17.40°, 18.00°, 18.70°, 20.16°, 20.62°, 21.90°, 23.50°, 24.78°, 25.18°, 34.08°, 36.72° and 38.04° (crystal C);
a polymorph which has specific peaks at a reflection angle 2θ of about 8.32°, 9.68°, 12.92°, 16.06°, 17.34°, 19.38°, 21.56°, 24.06°, 26.00°, 30.06°, 33.60° and 40.34° (crystal D).; and
a polymorph which has specific peaks at a reflection angle 2θ of about 6.86°, 8.36°, 9.60°, 11.76°, 13.74°, 14.60°, 15.94°, 16.74°, 17.56°, 20.00°, 21.26°, 23.72°, 24.78°, 25.14°, 25.74°, 26.06°, 26.64°, 27.92°, 28.60°, 29.66° and 29.98° (crystal G), and an amorphous (also referred to as crystal E).
In said International Publication WO99/65885, it is described that crystals A, C and G are useful in view of retention of a crystal form in long term storage. Among them, crystal A is preferred in view of industrial superiority.
However, the publication is silent about what the industrial superiority means. Further, the publication has no evidence (data) supporting the fact that the crystal A is preferred in view of industrial superiority.
The present inventors investigated this matter and found that, in formulating 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylic acid, it is not possible to obtain preparations having no variation in the dissolution profiles of drugs, even if such a crystal form is used as is thought to be most stable in a physical stability test. Further, they found that there is a crystal form that is suitable for preparing preparations, independently from the characteristics of the crystals (including amorphous) of drug substances and have reached the invention.
An object of the invention is, therefore, to provide solid preparations of 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolecarboxylic acid which is stable and which is little variation in the dissolution profiles.